The Role of the Piezo1 Mechanosensitive Channel in Heart Failure

Abstract

Mechanotransduction (MT) is inseparable from the pathobiology of heart failure (HF). However, the effects of mechanical forces on HF remain unclear. This review briefly describes how Piezo1 functions in HF-affected cells, including endothelial cells (ECs), cardiac fibroblasts (CFs), cardiomyocytes (CMs), and immune cells. Piezo1 is a mechanosensitive ion channel that has been extensively studied in recent years. Piezo1 responds to different mechanical forces and converts them into intracellular signals. The pathways that modulate the Piezo1 switch have also been briefly described. Experimental drugs that specifically activate Piezo1-like proteins, such as Yoda1, Jedi1, and Jedi2, are available for clinical studies to treat Piezo1-related diseases. The only mechanosensitive ion-channel-specific inhibitor available is GsMTx4, which can turn off Piezo1 by modulating the local membrane tension. Ultrasound waves can modulate Piezo1 switching in vitro with the assistance of microbubbles. This review provides new possible targets for heart failure therapy by exploring the cellular functions of Piezo1 that are involved in the progression of the disease. Modulation of Piezo1 activity may, therefore, effectively delay the progression of heart failure.